Using Mendelian Randomization to Study the Role of Iron in Health and Disease

Zeitoun, Tara; El-Sohemy, Ahmed

doi:10.3390/ijms241713458

Cited by 11 publications

(4 citation statements)

References 89 publications

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“…Iron de ciency may result in restricted erythropoiesis, consequently precipitating iron de ciency anemia. Conversely, an overabundance of iron is similarly detrimental, given that surplus labile iron augments reactive oxygen species levels, culminating in ferroptosis 8,9 . Currently, the role of iron in IVDD remains controversial.…”

Section: Introductionmentioning

confidence: 99%

No Genetic Causal Association between Iron Status and Intervertebral Disc Degeneration: A Two-Sample Mendelian Randomization Study

Li,

Su,

et al. 2024

Preprint

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Many clinical and basic studies have shown an association between iron status and intervertebral disc degeneration (IVDD). However, their causal relationship is still unclear. The aim of this study was to explore the genetic causality between iron status and IVDD using Mendelian randomization. Random effects inverse variance weighted (IVW) meta-analysis was the primary method of analysis, with MR‒Egger, weighted median, simple modal, and weighted modal methods as secondary methods. Subsequently, we used IVW, MR‒Egger, MR-PRESSO, and leave-one-out analyses to test for heterogeneity and horizontal pleiotropy. Finally, we used the maximum likelihood, penalized weighted median and IVW (fixed effects) methods to further verify the reliability of the results. Random-effects IVW and IVW meta-analyses revealed that transferrin, total iron binding capacity (TIBC), ferritin, iron, and transferrin saturation (TSAT) were not genetically causally related to IVDD, and removal of outliers detected by MR-PRESSO resulted in broad consistency. Our study revealed that there is no genetic causal relationship between iron status and IVDD, but it cannot be excluded that there is a correlation between the two at a level other than genetics.

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Section: Introductionmentioning

confidence: 99%

No Genetic Causal Association between Iron Status and Intervertebral Disc Degeneration: A Two-Sample Mendelian Randomization Study

Li,

Su,

et al. 2024

Preprint

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“…Assessing the role of risk factors in health and disease using MR has emerged as an important approach to obtaining new evidence. 16 Thus, to reveal the potential bidirectional causal association between stroke and VLUs, we performed a MR analysis in this study.…”

Section: Introductionmentioning

confidence: 99%

“…MR has the advantage of overcoming the limitations of traditional observational studies without the high cost of randomized controlled trials. Assessing the role of risk factors in health and disease using MR has emerged as an important approach to obtaining new evidence 16 . Thus, to reveal the potential bidirectional causal association between stroke and VLUs, we performed a MR analysis in this study.…”

Section: Introductionmentioning

confidence: 99%

Association between stroke and venous leg ulcers: A Mendelian randomization study

Xie,

Han,

Liu

et al. 2024

International Wound Journal

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To investigate any potential bidirectional causal relationships between stroke and venous leg ulcers (VLUs), Mendelian randomization (MR) analyses were carried out in this study. The exposure factor was stroke, the outcome factor was VLUs. The two‐sample MR study was carried out based on the online analysis platform (http://app.mrbase.org/). The association of stroke and VLUs was analysed via methods of Inverse Variance Weighted (IVW), Weighted Median, MR‐Egger and weighted mode. IVW method suggested no association between stroke and VLUs ((β 1.06; SE 9.321; p = 0.9095)). Weighted median estimator (β 5.906; SE 11.99, p = 0.6223), MR‐Egger (β −0.8677; SE 21.89; p = 0.9691) and weighted mode (β 9.336; SE 17.77; p = 0.6089) showed consistent results. Conversely, evidence indicating that the presence of VLUs increased the risk of stroke was lacking. According to this MR study, there is no causal connection between stroke and VLUs, which suggests that therapies targeting stroke may not be effective against VLUs.

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“…Iron is an essential mineral with oxidative-reductive potential [ 29 ]. It plays an important role in preserving physiological functions, including oxygen transport, free radical homeostasis, the immune system, cognitive function, cellular metabolism, and enzyme function [ 30 , 31 ]. The mitochondrial reactions that produce the adenosine triphosphate that is responsible for promoting spermatogenesis and sperm motility require oxygen to function [ 32 , 33 ].…”

Section: Introductionmentioning

confidence: 99%

Biomarkers of Iron Are Associated with Anterior-Pituitary-Produced Reproductive Hormones in Men with Infertility

Rastegar Panah,

Jarvi,

et al. 2024

Nutrients

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Approximately 16% of North American couples are affected by infertility, with 30% of cases being attributable to male factor infertility. The regulation of reproductive hormones via the hypothalamic–pituitary–gonadal axis is important for spermatogenesis and subsequently male fertility. Maintaining iron homeostasis is critical to normal reproductive physiological function. This cross-sectional study’s objective was to determine the association between serum biomarkers of iron and reproductive hormones. Men experiencing infertility (n = 303) were recruited from Mount Sinai Hospital, Toronto. Serum was analyzed for iron and ferritin as biomarkers of iron status and reproductive hormones (follicle-stimulating hormone, luteinizing hormone, testosterone, estradiol, and prolactin), which were the primary outcome. Associations were determined using non-parametric Spearman’s rank correlation coefficient, linear regressions, and logistic regressions. A significant independent monotonic inverse relationship between serum iron and prolactin (p = 0.0002) was found. In linear regression analyses, iron was inversely associated with luteinizing hormone (unadjusted p = 0.03, adjusted p = 0.03) and prolactin (unadjusted p = 0.001 and adjusted p = 0.003). Serum ferritin was inversely associated with both gonadotropins, follicle-stimulating hormone (adjusted p = 0.03), and luteinizing hormone (adjusted p = 0.02). These findings suggest that biomarkers of iron are associated with pituitary-produced reproductive hormones, which play a role in the hypothalamic–pituitary–gonadal signaling pathway involved in spermatogenesis, testicular testosterone production, and male fertility.

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Using Mendelian Randomization to Study the Role of Iron in Health and Disease

Cited by 11 publications

References 89 publications

No Genetic Causal Association between Iron Status and Intervertebral Disc Degeneration: A Two-Sample Mendelian Randomization Study

No Genetic Causal Association between Iron Status and Intervertebral Disc Degeneration: A Two-Sample Mendelian Randomization Study

Association between stroke and venous leg ulcers: A Mendelian randomization study

Biomarkers of Iron Are Associated with Anterior-Pituitary-Produced Reproductive Hormones in Men with Infertility

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